The great Roman natural scientist Gaius Plinius Secundus (Pliny the Elder) in his comprehensive study of about 60 A.D. first described a most potent Indian Ocean sea hare of the genus Dolabella. [The Romans first designated Mollusca of the family Aplysidae as sea hares due to a similarity between the ears of a hare and the auriculate tentacles of these gastropods. Consult article by N. B. Eales, L.M.B.C. Memoirs, Vol. XXIV. on "Typical British Marine Plants and Animals," in Aplysia, edited by W. A. Hardman and J. Johnstone, (Liverpool University Press, 1921)]. Extracts from this animal and two related Aplysia species from the Mediterranean were well known for their toxic properties during the reign of Nero [Pliny, Historia Naturalis, Lib. IX., Lib. XXXII, ca. 60 A.D. and N. B. Eales, supra]. By 150 A.D. Nicander [N. B. Eales, supra] recognized the possibility of using such extracts for treatment of certain diseases. However, the potential of the Indian Ocean Dolabella with respect to modern medical problems was not recognized until the subject invention wherein extremely active anticancer constituents are isolated from the Indian Ocean Dolabella auricularia [The D. auricularia was probably the first described by Pliny and the minor variations recorded in subsequent literature as e.g., D. andersonii, D. californica, D. ecaudata, and D. scapula are actually one species, namely D. auricularia, see H. Engel, Zool. Med. Museum Leiden, 24, (1945)].
The dolastatins may correspond to the potent D. auricularia constituents recognized from ancient to fairly recent times [1969 Ph.D. dissertation of M. Watson, U. of Hawaii, "Some Aspects of the Pharmacology, Chemistry and Biology of the Midgut Gland Toxins of Some Hawaiian Sea Hares, especially Dolabella auricularia and Aplysia pulmonica," University Microfilms Inc., Ann Arbor, Michigan]. Since dolastatin 1 has been shown by the U.S. National Cancer Institute to cause an 88% life extension with the murine P388 lymphocytic leukemia, and a 30% curative response against the murine B16 melanoma at intraperitoneal doses of 11 .mu.g/kg/day, it may represent the most active (lowest dose) presently known antineoplastic agent.